Sjogren's syndrome is a chronic autoimmune disorder characterized by mononuclear infiltration of the lacrimal and salivary glands. This leads to destruction of the glandular structures with subsequent keratoconjunctivitis sicca and xerostomia. Ocular involvement may lead to damage of the vital structures of the eye eventuating in distressing symptoms and major visual impairment. In this proposal, we are employing an animal model of autoimmune disease similar to that of Sjogren's syndrome. This natural animal model represented by the NZB/NZE F1 hybrid mice develops many of the features seen in the human disease. A systematic study is undertaken to evaluate the histopathologic and immunopathologic changes in the lacrimal glands of this animal model. We shall also study the effects of immunologic and hormonal modulation on the course of the disease and on the histopathology of the lacrimal gland. Certain immunologic parameters will be evaluted including the determination of antibodies to DNA and RNA, skin allograft rejection in vivo, lymphocyte stimulation, antibody to sheep red blood cells, mixed lymphocyte reactions. Sections of lacrimal glandular tissues will be evaluated by light microscopy and immunofluorescence technique. We shall correlate the results of the immunologic parameters with histopathologic observations on the lacrimal glands. In addition, the hormonal influences on the lacrimal gland will be studied in the NZB/NZW F1 hybrid mice. This project would also investigate certain therapeutic regimens and newer noninvasive diagnostic procedures in patients suffering from Sjogren's syndrome. New immunologic techniques will be employed to detect subtle changes in tear microsamples.